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Gluten-free diet

Wheat

A gluten-free diet (GFD) is a diet that strictly excludes gluten, which is a mixture of proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats.[1] The inclusion of oats in a gluten-free diet remains controversial, and may depend on the oat cultivar and the frequent cross-contamination with other gluten-containing cereals.[2][3][4][5]

Gluten proteins have low nutritional and biological value, and the grains that contain gluten are not essential in the human diet.[16] However, an unbalanced selection of food and an incorrect choice of gluten-free replacement products may lead to nutritional deficiencies. Replacing flour from wheat or other gluten-containing cereals with gluten-free flours in commercial products may lead to a lower intake of important nutrients, such as iron and B vitamins. Some gluten-free commercial replacement products are not enriched or fortified as their gluten-containing counterparts, and often have greater lipid/carbohydrate content. Children especially often over-consume these products, such as snacks and biscuits. Nutritional complications can be prevented by a correct dietary education.[4]

A gluten-free diet should be mainly based on naturally gluten-free foods with a good balance of micro and macro nutrients: meat, fish, eggs, milk and dairy products, legumes, nuts, fruits, vegetables, potatoes, rice, and corn are all appropriate components of such a diet.[17] If commercially prepared, gluten-free replacement products are used, choosing those that are enriched or fortified with vitamins and minerals is preferable.[4]Pseudocereals (quinoa, amaranth, and buckwheat) and some minor cereals are healthy alternatives to these prepared products and have high biological and nutritional value.[4][16] Furthermore, they contain protein of higher nutritional quality than those of wheat, and in greater quantities.[4]

Coeliac disease

Coeliac disease (American English: celiac) (CD) is a chronic, immune-mediated, and mainly intestinal process, caused by the ingestion of wheat, barley, rye and derivatives, that appears in genetically predisposed people of all ages. CD is not only a gastrointestinal disease, because it may affect several organs and cause an extensive variety of non-gastrointestinal symptoms, and most importantly, it may often be completely asymptomatic. Added difficulties for diagnosis are the fact that serological markers (anti-tissue transglutaminase [TG2]) are not always present[24] and many people with coeliac may have minor mucosal lesions, without atrophy of the intestinal villi.[25]

CD with “classic symptoms”, which include gastrointestinal manifestations such as chronic diarrhoea and abdominal distention, malabsorption, loss of appetite, and impaired growth, is currently the least common presentation form of the disease and affects predominantly to small children generally younger than two years of age.[28][30]

CD with “non-classic symptoms” is the most common clinical type and occurs in older children (over 2 years old), adolescents and adults.[30] It is characterized by milder or even absent gastrointestinal symptoms and a wide spectrum of non-intestinal manifestations that can involve any organ of the body, and very frequently may be completely asymptomatic[28] both in children (at least in 43% of the cases[34]) and adults.[28]

Following a lifelong gluten-free diet is the only medically-accepted treatment for people with coeliac disease.[16][35]

Non-coeliac gluten sensitivity

Non-coeliac gluten sensitivity (NCGS) is described as a condition of multiple symptoms that improves when switching to a gluten-free diet, after coeliac disease and wheat allergy are excluded.[36][37] People with NCGS may develop gastrointestinal symptoms, which resemble those of irritable bowel syndrome (IBS)[38][39] or a variety of nongastrointestinal symptoms.[20][40][41]

The pathogenesis of NCGS is not yet well understood. For this reasons, it is a controversial syndrome[44] and some authors still question it.[45] There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system.[40][46]FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in persons with NCGS.[40][47][46][48] As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they only explain certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.[46][49][40]

After exclusion of coeliac disease and wheat allergy,[50] the subsequent step for diagnosis and treatment of NCGS is to start a strict gluten-free diet to assess if symptoms improve or resolve completely. This may occur within days to weeks of starting a GFD, but improvement may also be due to a non-specific, placebo response.[51] Recommendations may resemble those for coeliac disease, for the diet to be strict and maintained, with no transgression.[20] The degree of gluten cross contamination tolerated by people with NCGS is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts.[20] It is not yet known whether NCGS is a permanent or a transient condition.[20][44] A trial of gluten reintroduction to observe any reaction after 1–2 years of strict gluten-free diet might be performed.[20]

A subgroup of people with NCGS may not improve by eating commercially available gluten-free products, which are usually rich of preservatives and additives, because chemical additives (such as sulphites, glutamates, nitrates and benzoates) might have a role in evoking functional gastrointestinal symptoms of NCGS. These people may benefit from a diet with a low content of preservatives and additives.[47]

NCGS, which is possibly immune-mediated, now appears to be more common than coeliac disease,[52] with prevalence rates between 0.5–13% in the general population.[53]

Wheat allergy

People can also experience adverse effects of wheat as result of a wheat allergy.[29] Gastrointestinal symptoms of wheat allergy are similar to those of coeliac disease and non-coeliac gluten sensitivity, but there is a different interval between exposure to wheat and onset of symptoms. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and could be anaphylaxis.[24][54]

The management of wheat allergy consists of complete withdrawal of any food containing wheat and other gluten-containing cereals.[8][54] Nevertheless, some people with wheat allergy can tolerate barley, rye or oats.[55]

Gluten ataxia

A male with gluten ataxia: previous situation and evolution after 3 months of gluten-free diet.

Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten.[56] With gluten ataxia, damage takes place in the cerebellum, the balance center of the brain that controls coordination and complex movements like walking, speaking and swallowing, with loss of Purkinje cells. People with gluten ataxia usually present gait abnormality or incoordination and tremor of the upper limbs. Gaze-evoked nystagmus and other ocular signs of cerebellar dysfunction are common. Myoclonus, palatal tremor, and opsoclonus-myoclonus may also appear.[57]

Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible.[57][58]

Gluten ataxia accounts for 40% of ataxias of unknown origin and 15% of all ataxias.[57][59] Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage.[57]

As a fad diet

Since the beginning of the 21st century, the gluten-free diet has become the most popular fad diet in the United States and other countries.[40] Clinicians worldwide have been challenged by an increasing number of people who do not have coeliac disease nor wheat allergy, with digestive or extra-digestive symptoms which improved removing wheat/gluten from the diet. Many of these persons began a gluten-free diet on their own, without having been previously evaluated.[60][61] Another reason that contributed to this trend was the publication of several books that demonize gluten and point to it as a cause of type 2 diabetes, weight gain and obesity, and a broad list of diseases ranging from depression and anxiety to arthritis and autism.[62][63] The book that has had the most impact is Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar – Your Brain’s Silent Killers, by the American neurologist David Perlmutter, published in September 2013.[62] Another book that has had great impact is Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health, by the cardiologist William Davis, which refers to wheat as a “chronic poison” and became a New York Times bestseller within a month of publication in 2011.[64] The gluten-free diet has been advocated and followed by many celebrities to lose weight, such as Miley Cyrus, Gwyneth Paltrow, and Kourtney Kardashian, and are used by some professional athletes, who believe the diet can improve energy and health.[65][66][67][68] It became popular in USA, as the popularity of low-carbohydrate diets faded.[69]

Estimates suggest that in 2014, 30% of people in USA and Australia were consuming gluten-free foods, with a growing number, calculated from surveys that by 2016 approximately 100 million Americans would consume gluten-free products.[40][62][70] Data from a 2015 Nielsen survey of 30,000 adults in 60 countries around the world conclude that 21% of people prefer to buy gluten-free foods, being the highest interest among the younger generations.[71] In USA, it was estimated that more than half of people who buy foods labeled gluten-free do not have a clear reaction to gluten, and they do so “because they think it will help them lose weight, because they seem to feel better or because they mistakenly believe they are sensitive to gluten.”[72] Although gluten is highly immunologically reactive and humans appear not to have evolved to digest it well, a gluten-free diet is not a healthier option for the general population, other than people suffering from gluten-related disorders or other associated conditions which improve with a gluten-free diet in some cases, such as irritable bowel syndrome and certain autoimmune and neurological disorders.[12][73][74] There is no published experimental evidence to support that the gluten-free diet contributes to weight loss.[74]

In a review of May 2015 published in Gastroenterology, Fasano et al. conclude that, although there is an evident “fad component” to the recent rise in popularity of the gluten-free diet, there is also growing and unquestionable evidence of the existence of non-coeliac gluten sensitivity.[75]

The popularity of the gluten-free diet is hurting people who actually need to eliminate gluten due to medical reasons. The servers are issuing judgments, believing that it is simply a fad, which is leading to them not taking the necessary precautions in the handling of the food to avoid gluten cross-contamination. “In other words, the customers who ‘order gluten-free meals washed down with a gluten-filled beer’ are essentially making a mockery of a serious issue”.[76] Even many professionals in the medical field think that the gluten-free diet is just a fad.[73] On the other hand, the popularity of the gluten-free diet has increased the availability of commercial gluten-free replacement products and gluten-free grains.[74]

Gluten-free commercial replacement products, such as gluten-free cakes, are more expensive than their gluten-containing counterparts, so their purchase adds a financial burden.[30] They are also typically higher in calories, fat, and sugar, and lower in dietary fibre.[69] In less developed countries, wheat can represent an important source of protein, since it is a substantial part of the diet in the form of bread, noodles, bulgur, couscous, and other products.[16][77]

In the British National Health Service gluten free foods have been supplied on prescription. For many patients this meant at no cost. When it was proposed to alter this in 2018 the Department of Health and Social Care made an assessment of the costs and benefits. The potential annual financial saving to the service was estimated at £5.3 million, taking into account the reduction in cost spending and the loss of income from prescription charges. The proposed scenario was actually that patients could still be prescribed gluten free breads and mixes but would have to buy any other gluten free products themselves the savings would only amount to £700,000 a year. Local initiatives by clinical commissioning groups had already reduced the cost of gluten free foods to the NHS by 39% between 2015 and 2017.[78]

Healthcare professionals recommend against undertaking a gluten-free diet as a form of self-diagnosis,[79] because tests for coeliac disease are reliable only if the person has been consuming gluten recently. There is a consensus in the medical community that people should consult a physician before going on a gluten-free diet, so that a medical professional can accurately test for coeliac disease or any other gluten-induced health issues.[80]

Research

In a 2013 double-blind, placebo-controlled challenge (DBPC) by Biesiekierski et al. in a few people with irritable bowel syndrome, the authors found no difference between gluten or placebo groups and the concept of non-celiac gluten sensitivity as a syndrome was questioned. Nevertheless, this study had design errors and an incorrect selection of participants, and probably the reintroduction of both gluten and whey protein had a nocebo effect similar in all people, and this could have masked the true effect of gluten/wheat reintroduction.[29][42]

In a 2018 double-blind, crossover research study on 59 persons on a gluten-free diet with challenges of gluten, fructans or placebo, intestinal symptoms (specifically bloating) were borderline significantly higher after challenge with fructans, in comparison with gluten proteins (P=0.049).[46][49] Although the differences between the three interventions was very small, the authors concluded that fructans (the specific type of FODMAP found in wheat) are more likely to be the cause of gastrointestinal symptoms of non-celiac gluten sensitivity, rather than gluten.[46] In addition, fructans used in the study were extracted from chicory root, so it remains to be seen whether the wheat fructans produce the same effect.[49]

Eating gluten-free

Gluten-free bread made of a mixture of flours like buckwheat flour, tapioca flour, millet flour and psyllium seed husks. Special flour mixes can be bought for bread-making purposes.

A gluten-free diet is a diet that strictly excludes gluten, proteins present in wheat (and all wheat varieties such as spelt and kamut), barley, rye, oat, and derivatives of these grains such as malt and triticale, and foods that may include them, or shared transportation or processing facilities with them.[1][17] The inclusion of oats in a gluten-free diet remains controversial.[1]Oat toxicity in people with gluten-related disorders depends on the oat cultivar consumed because the immunoreactivities of toxic prolamins are different among oat varieties.[4][3] Furthermore, oats are frequently cross-contaminated with the other gluten-containing cereals.[4] Pure oat (labelled as “pure oat” or “gluten-free oat”[2]) refers to oats uncontaminated with any of the other gluten-containing cereals.[3] Some cultivars of pure oat could be a safe part of a gluten-free diet, requiring knowledge of the oat variety used in food products for a gluten-free diet.[3] Nevertheless, the long-term effects of pure oats consumption are still unclear[81] and further studies identifying the cultivars used are needed before making final recommendations on their inclusion in the gluten-free diet.[5]

Other grains, although gluten-free in themselves, may contain gluten by cross-contamination with gluten-containing cereals during grain harvesting, transporting, milling, storing, processing, handling or cooking.[82][83]

Cross contamination in the home is also a consideration for those who suffer gluten-related disorders.[22][10] There can be many sources of cross contamination, as for example when family members prepare gluten-free and gluten-containing foods on the same surfaces (counter tops, tables, etc.) or share utensils that have not been cleaned after being used to prepare gluten-containing foods (cutting boards, colanders, cutlery, etc.), kitchen equipment (toaster, cupboards, etc.) or certain packaged foods (butter, peanut butter, etc.).[10]

Risks

An unbalanced selection of food and an incorrect choice of gluten-free replacement products may lead to nutritional deficiencies. Replacing flour from wheat or other gluten-containing cereals with gluten-free flours in commercial products may lead to a lower intake of important nutrients, such as iron and B vitamins and a higher intake of sugars and saturated fats. Some gluten-free commercial replacement products are not enriched or fortified as their gluten-containing counterparts, and often have greater lipid / carbohydrate content. Children especially often over-consume these products, such as snacks and biscuits. These nutritional complications can be prevented by a correct dietary education.[4]Pseudocereals (quinoa, amaranth, and buckwheat) and some minor cereals are healthy alternatives to these prepared products and have higher biological and nutritional value.[4][16] Advances towards higher nutrition-content gluten-free bakery products, improved for example in terms of fiber content and glycemic index, have been made by using not exclusively corn starch or other starches to substitute for flour. In this aim, for example the dietary fibre inulin (which acts as a prebiotic[87]) or quinoa or amaranth wholemeal have been as substitute for part of the flour. Such substitution has been found to also yield improved crust and texture of bread.[88] It is recommended that anyone embarking on a gluten-free diet check with a registered dietitian to make sure they are getting the required amount of key nutrients like iron, calcium, fiber, thiamin, riboflavin, niacin and folate. Vitamins often contain gluten as a binding agent. Experts have advised that it is important to always read the content label of any product that is intended to be swallowed.[89]

Up to 30% of people with known coeliac disease often continue having or redeveloping symptoms.[10][90] Also, a lack of symptoms or negative blood antibodies levels are not reliable indicators of intestinal recuperation. Several studies show an incomplete recovery of small bowel despite a strict gluten-free diet, and about 79% of such people have persistent villous atrophy.[10] This lack of recovery is mainly caused by inadvertent exposure to gluten.[10][90] People with poor basic education and understanding of the gluten-free diet often believe that they are strictly following the diet, but are making regular errors.[11][10] In addition, some people often deliberately continue eating gluten because of limited availability, inferior taste, higher price, and inadequate labelling of gluten-free products. Poor compliance with the regimen is also influenced by age at diagnosis (adolescents), ignorance of the consequences of the lack of a strict treatment and certain psychological factors.[10] Ongoing gluten intake can cause severe disease complications, such as various types of cancers (both intestinal and extra-intestinal) and osteoporosis.[10][90]

Regulation and labels

The term gluten-free is generally used to indicate a supposed harmless level of gluten rather than a complete absence.[18] The exact level at which gluten is harmless is uncertain and controversial. A 2008 systematic review tentatively concluded that consumption of less than 10 mg (10 ppm) of gluten per day is unlikely to cause histological abnormalities, although it noted that few reliable studies had been done.[18]

Regulation of the label gluten-free varies by country. Most countries derive key provisions of their gluten-free labelling regulations from the Codex Alimentariusinternational standards for food labelling as a standard relating to the labelling of products as gluten-free. It only applies to foods that would normally contain gluten.[91] Gluten-free is defined as 20 ppm (= 20 mg/kg) or less. It categorizes gluten-free food as:

Food that is gluten-free by composition

Food that has become gluten-free through special processing.

Reduced gluten content, food which includes food products with between 20 and 100 ppm of gluten Reduced gluten content is left up to individual nations to more specifically define.

The Codex Standard suggests the enzyme-linked Immunoassay (ELISA) R5 Mendez method for indicating the presence of gluten, but allows for other relevant methods, such as DNA. The Codex Standard specifies that the gluten-free claim must appear in the immediate proximity of the name of the product, to ensure visibility.

There is no general agreement on the analytical method used to measure gluten in ingredients and food products.[92] The ELISA method was designed to detect w-gliadins, but it suffered from the setback that it lacked sensitivity for barley prolamins.[93] The use of highly sensitive assays is mandatory to certify gluten-free food products. The European Union, World Health Organization, and Codex Alimentarius require reliable measurement of the wheat prolamins, gliadins rather than all-wheat proteins.[94]

Australia

food labelled gluten-free include no detectable gluten (<3ppm [96]) oats or their products, cereals containing gluten that have been malted or their products

food labelled low gluten claims such that the level of 20 mg gluten per 100 g of the food

Brazil

All food products must be clearly labelled whether they contain gluten or they are gluten-free.[97] Since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the Good Manufacturing Practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts.[98] When a product contains the warning of cross-contamination with wheat, rye, barley, oats and their hybridised strains, the warning “contains gluten” is mandatory. The law does not establish a gluten threshold for the declaration of its absence.[97]

Canada

Health Canada considers that foods containing levels of gluten not exceeding 20 ppm as a result of contamination, meet the health and safety intent of section B.24.018 of the Food and Drug Regulations when a gluten-free claim is made.[99] Any intentionally added gluten, even at low levels must be declared on the packaging and a gluten-free claim would be considered false and misleading. Labels for all food products sold in Canada must clearly identify the presence of gluten if it is present at a level greater than 10 ppm.[100]

European Union

All foods containing gluten as an ingredient must be labelled accordingly as gluten is defined as one of the 14 recognised EU allergens.[102]

United States

Until 2012 anyone could use the gluten-free claim with no repercussion.[citation needed] In 2008, Wellshire Farms chicken nuggets labelled gluten-free were purchased and samples were sent to a food allergy laboratory[103] where they were found to contain gluten. After this was reported in the Chicago Tribune, the products continued to be sold. The manufacturer has since replaced the batter used in its chicken nuggets.[104] The U.S. first addressed gluten-free labelling in the 2004 Food Allergen Labeling and Consumer Protection Act (FALCPA). The Alcohol and Tobacco Tax and Trade Bureau published interim rules and proposed mandatory labelling for alcoholic products in 2006.[105] The FDA issued their Final Rule on August 5, 2013.[106]
When a food producer voluntarily chooses to use a gluten-free claim for a product, the food bearing the claim in its labelling may not contain:

an ingredient that is a gluten-containing grain

an ingredient that is derived from a gluten-containing grain that has not been processed to remove gluten

an ingredient that is derived from a gluten-containing grain, that has been processed to remove gluten but results in the presence of 20 ppm or more gluten in the food. Any food product claiming to be gluten-free and also bearing the term “wheat” in its ingredient list or in a separate “Contains wheat” statement, must also include the language “*the wheat has been processed to allow this food to meet the FDA requirements for gluten-free foods,” in close proximity to the ingredient statement.

Any food product that inherently does not contain gluten may use a gluten-free label where any unavoidable presence of gluten in the food bearing the claim in its labelling is below 20 ppm gluten.

See also

References

^ abcdBiesiekierski JR (2017). “What is gluten?”. J Gastroenterol Hepatol (Review). 32 Suppl 1: 78–81. doi:10.1111/jgh.13703. PMID28244676. Similar proteins to the gliadin found in wheat exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as “gluten.” Derivatives of these grains such as triticale and malt and other ancient wheat varieties such as spelt and kamut also contain gluten. The gluten found in all of these grains has been identified as the component capable of triggering the immune-mediated disorder, coeliac disease.

^ abcdComino I, Moreno Mde L, Sousa C (November 7, 2015). “Role of oats in celiac disease”. World J Gastroenterol. 21 (41): 11825–31. doi:10.3748/wjg.v21.i41.11825. PMC4631980. PMID26557006. It is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.

^ abcdefghiPenagini F, Dilillo D, Meneghin F, Mameli C, Fabiano V, Zuccotti GV (November 18, 2013). “Gluten-free diet in children: an approach to a nutritionally adequate and balanced diet”. Nutrients. 5 (11): 4553–65. doi:10.3390/nu5114553. PMC3847748. PMID24253052. For CD patients on GFD, the nutritional complications are likely to be caused by the poor nutritional quality of the GFPs mentioned above and by the incorrect alimentary choices of CD patients. (…) the limited choice of food products in the diet of children with CD induces a high consumption of packaged GFPs, such as snacks and biscuits. (..) It has been shown that some commercially available GFPs have a lower content of folates, iron and B vitamins or are not consistently enriched/fortified compared to their gluten containing counterparts. (…) The first step towards a balanced diet starts from early education on CD and GFD, possibly provided by a skilled dietitian and/or by a physician with expert knowledge in CD. (…) It is advisable to prefer consumption of naturally GF foods, since it has been shown that they are more balanced and complete under both the macro- and micro-nutrient point of view. In fact, these foods are considered to have a higher nutritional value in terms of energy provision, lipid composition and vitamin content as opposed to the commercially purified GF products. Within the range of naturally GF foods, it is preferable to consume those rich in iron and folic acid, such as leafy vegetables, legumes, fish and meat. During explanation of naturally GF foods to patients, it is a good approach for healthcare professionals to bear in mind the local food habits and recipes of each country. This may provide tailored dietary advice, improving acceptance and compliance to GFD. Furthermore, increasing awareness on the availability of the local naturally GF foods may help promote their consumption, resulting in a more balanced and economically advantageous diet. Indeed, these aspects should always be addressed during dietary counseling. With regards to the commercially purified GFPs, it is recommended to pay special attention to the labeling and chemical composition. (…) Increasing awareness on the possible nutritional deficiencies associated with GFD may help healthcare professionals and families tackle the issue by starting from early education on GFD and clear dietary advice on how to choose the most appropriate gluten-free foods.

^Volta U, Caio G, De Giorgio R, Henriksen C, Skodje G, Lundin KE (June 2015). “Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders”. Best Pract Res Clin Gastroenterol. 29 (3): 477–91. doi:10.1016/j.bpg.2015.04.006. PMID26060112. A recently proposed approach to NCGS diagnosis is an objective improvement of gastrointestinal symptoms and extra-intestinal manifestations assessed through a rating scale before and after GFD. Although a standardized symptom rating scale is not yet applied worldwide, a recent study indicated that a decrease of the global symptom score higher than 50% after GFD can be regarded as confirmatory of NCGS (Table 1) [53]. (…) After the confirmation of NCGS diagnosis, according to the previously mentioned work-up, patients are advized to start with a GFD [49].

^ abEl-Chammas K, Danner E (June 2011). “Gluten-free diet in nonceliac disease”. Nutr Clin Pract (Review). 26 (3): 294–9. doi:10.1177/0884533611405538. PMID21586414. The prescription of a GFD has been recommended for patients with IBS-like symptoms without histologic evidence of CD and who have positive IgA tTG antibodies or have the at-risk haplotypes DQ2 or DQ8.46 (…) Historically, a GFD was occasionally used in the management of multiple sclerosis (MS), because anecdotal reports indicated a positive effect (reversal of symptoms) of a GFD in MS patients. (…) what has been demonstrated so far is that a glutenfree vegan diet for 1 year significantly reduced disease activity and levels of antibodies to β-lactoglobulin and gliadin in patients with RA. (…) The beneficial effect of a GFD on diarrhea and weight gain in patients with HIV enteropathy has been demonstrated in a few case series. Treatment with a GFD has been observed to decrease the frequency of diarrhea and thus allow weight gain.84 (IBS=irritable bowel syndrome; RA=rheumatoid arthritis; GFD=gluten-free diet)

^ abBuie T (2013). “The relationship of autism and gluten”. Clin Ther (Review). 35 (5): 578–83. doi:10.1016/j.clinthera.2013.04.011. PMID23688532. At this time, the studies attempting to treat symptoms of autism with diet have not been sufficient to support the general institution of a gluten-free or other diet for all children with autism. …There may be a subgroup of patients who might benefit from a gluten-free diet, but the symptom or testing profile of these candidates remains unclear.

^Hadjivassiliou M, Grünewald RA, Davies-Jones GA (2002). “Gluten sensitivity as a neurological illness”. J Neurol Neurosurg Psychiatry (Review). 72 (5): 560–3. PMC1737870. PMID11971034. Incomplete elimination of gluten from the diet may be enough to abolish gastrointestinal symptoms with recovery of the small bowel mucosa but is insufficient to arrest the state of heightened immunological responsiveness resulting in neuronal injury. There is a group of patients with CD “resistant” to gluten-free diet. This may reflect hypersensitivity to the minute amounts of gluten present in most “gluten-free” products.

^Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). “Nonceliac gluten sensitivity”. Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID25583468. One of the most controversial and highly debated discussions concerns the role of gluten in causing NCGS. Recent reports have indicated that gluten might not be the cause of NCGS, and some investigators still question whether NCGS as a real clinical entity. (…) Cereals such as wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs in the daily diet (Table 1). Therefore, gluten-containing grains are not likely to induce IBS exclusively via FODMAPs. In contrast, there is growing evidence that other proteins that are unique to gluten-containing cereals can elicit an innate immune response that leads to NCGS, raising a nomenclature issue. For this reason, wheat sensitivity, rather than gluten sensitivity, seems to be a more appropriate term, keeping in mind that other gluten-containing grains such as barley and rye also can trigger the symptoms.

^ abcdeVerbeke, K (February 2018). “Nonceliac Gluten Sensitivity: What Is the Culprit?”. Gastroenterology. 154 (3): 471–473. doi:10.1053/j.gastro.2018.01.013. PMID29337156. Although intolerance to fructans and other FODMAPs may contribute to NCGS, they may only explain gastrointestinal symptoms and not the extraintestinal symptoms observed in NCGS patients, such as neurologic dysfunction, psychological disturbances, fibromyalgia, and skin rash.15 Therefore, it is unlikely that they are the sole cause of NCGS.

^ abcVolta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A (March 2019). “Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations”. Gastroenterol Clin North Am (Review). 48 (1): 165–182. doi:10.1016/j.gtc.2018.09.012. PMC6364564. PMID30711208. Furthermore, a role for the FODMAP (eg, fructans) component of wheat as the sole trigger for symptoms is somewhat doubtful, because many patients with NCWS report resolution of symptoms after the withdrawal of wheat and related cereals, while continuing to ingest vegetables and fruits with high FODMAP content in their diets.59 On the whole, it is conceivable that more than one culprit may be involved in symptoms of NCWS (as they are currently defined), including gluten, other wheat proteins, and FODMAPs.60–62